Systems and methods for integrated electrochemical and electrical detection

ABSTRACT

An integrated sensing device is capable of detecting analytes using electrochemical (EC) and electrical (E) signals. The device introduces synergetic new capabilities and enhances the sensitivity and selectivity for real-time detection of an analyte in complex matrices, including the presence of high concentration of interferences in liquids and in gas phases.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national phase application under 35 U.S.C. §371 ofInternational Application No. PCT/US2008/064744 filed 23 May 2008, whichclaims priority to U.S. Provisional Patent Application Ser. No.60/939,738 entitled, “Systems and Methods for Integrated Electrochemicaland Electrical Detection” which was filed on May 23, 2007. The entiretext of each of the above-referenced disclosures is specificallyincorporated herein by reference without disclaimer.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to sensors and, moreparticularly, to systems and methods for integrated electrochemical andelectrical detection.

2. Description of Related Art

Electrochemical sensors have been used in various chemical and medicalapplications to detect concentrations of biological analyte. However,the inventors hereof have recognized that electrochemical detection isnot without problems. For example, when an insufficient concentration ofanalyte is provided, the current flowing between working and counterelectrodes of the sensor is undetectable. Because the amount of analytedetected is directly proportional to the current flowing through thesensor, small analyte concentration can result immeasurable.

Electrical sensors have also been used to determine analyteconcentrations by detecting molecular binding-induced conductance orimpedance changes in electrical materials (e.g., silicon, conductingpolymers, and carbon nanotubes). Unfortunately, the inventors hereofhave also identified many drawbacks of this technique. For instance, inaddition to their large dimensions and high manufacturing costs,electrical sensors are generally highly dependent on the environment(e.g. ionic strength), less specific and less accurate.

The referenced shortcomings are not intended to be exhaustive, butrather are among many that tend to impair the effectiveness ofpreviously known techniques as recognized by the present inventors.These problems are sufficient to demonstrate that the methodologiesappearing in the art have not been satisfactory, and that a significantneed exists for the techniques described and claimed in this disclosure.

SUMMARY OF THE INVENTION

An integrated sensing device is capable of detecting analytes usingelectrochemical (EC) and electrical (E) signals. The device introducessynergetic new capabilities and enhances the sensitivity and selectivityfor real-time detection of an analyte in complex matrices, including thepresence of high concentration of interferences in liquids and in gasphases.

In some embodiments, the invention relates to electrochemical-electrical(EC-E) sensors comprising: a first electrode fabricated on a substrate;a second electrode fabricated on the substrate and spaced apart from thefirst electrode; a bridging material coupling the first electrode to thesecond electrode; an electrolyte; a counter electrode; and a referenceelectrode; wherein at least one of the electrodes is connected to anelectronic circuit for electrochemical-electrical control and/ormeasurement during use.

In specific embodiments, the first electrode of the sensor is connectedto an electronic circuit for applying a potential perturbation to thefirst electrode during use. In some embodiments the electronic circuitis a biopotentiostat.

In some embodiments, one or more of the counter electrode, referenceelectrode, and/or bridging material is comprised on the substrate.However, in other embodiments one or more of these components will becomprised off the substrate.

In some specific embodiments, the sensor comprise a third electrodeplaced apart from the first and second electrodes. In some applications,the third electrode is employed for electrochemical control and/ormeasurement during use. Further, in embodiments with the thirdelectrode, the first and second electrodes may be employed forconductance measurement during use. In some cases, the electroniccircuit is a tripotentiostat.

The sensors can have a surface area ratio between the second electrodeand the first electrode allows an electrochemical process taking placeon the second electrode and electrical properties between the first andsecond electrodes to be controlled and/or measured simultaneously.

The bridging material may be any suitable material as understood by aperson of ordinary skill in the art, whether now existing or yet to bediscovered. For example, the bridging material may be, but it is notlimited to, a polymer, Si, GaAs, a metal oxide, other organic andinorganic semiconductors, a molecularly imprinted material, and/orcomposites made of polymers and conducting or semiconducting materials.Further, the bridging material may be provided in the form or ananotube, a nanowire, a nanoparticle, a nanorod, and/or a nanobelt.

In one particularly specific embodiment, an electrochemical-electrical(EC-E) sensor comprises a first electrode fabricated on a substrate andcoupled to a biopotentiostat circuit for applying a potentialperturbation to the first electrode, a second electrode fabricated onthe substrate and spaced apart from the first electrode, a bridgingmaterial fabricated on the substrate and coupling the first electrode tothe second electrode, a counter electrode fabricated on the substrateand operable to close an electric circuit, and a reference electrodefabricated on the substrate and operable to control a potential of atleast one of the first and second electrodes. A surface area ratiobetween the second electrode and the first electrode allows anelectrochemical process taking place on the second electrode andelectrical properties between the first and second electrodes to bemeasured simultaneously.

Some aspects of the invention relate to methods comprising: providing anEC-E sensor as described above or in the claims; providing an analyte;detecting a byproduct; determining a conductance and/or electricalcurrent of the conducting or semiconducting material; determining anelectrochemical signal; and detecting the analyte employing theconductance and the electrochemical signal. In some embodiments, theconductance and/or electrical current can be measured using the firstelectrode. Further, in some embodiments, the electrochemical signal ismeasured using the second electrode. Such methods may further compriseadjusting the surface area ratio between the second electrode and thefirst electrode to optimize performance of the EC-E sensor. In somecases the may comprise a molecule in gas phase; in others, the analytemay comprises a molecule in liquid phase.

The term “coupled” is defined as connected, although not necessarilydirectly, and not necessarily mechanically.

The terms “a” and “an” are defined as one or more unless this disclosureexplicitly requires otherwise.

The term “substantially,” “about,” and their variations are defined asbeing largely but not necessarily wholly what is specified as understoodby one of ordinary skill in the art, and in one non-limiting embodiment,the substantially refers to ranges within 10%, preferably within 5%,more preferably within 1%, and most preferably within 0.5% of what isspecified.

The terms “comprise” (and any form of comprise, such as “comprises” and“comprising”), “have” (and any form of have, such as “has” and“having”), “include” (and any form of include, such as “includes” and“including”) and “contain” (and any form of contain, such as “contains”and “containing”) are open-ended linking verbs. As a result, a method ordevice that “comprises,” “has,” “includes” or “contains” one or moresteps or elements possesses those one or more steps or elements, but isnot limited to possessing only those one or more elements. Likewise, astep of a method or an element of a device that “comprises,” “has,”“includes” or “contains” one or more features possesses those one ormore features, but is not limited to possessing only those one or morefeatures. Furthermore, a device or structure that is configured in acertain way is configured in at least that way, but may also beconfigured in ways that are not listed.

Other features and associated advantages will become apparent withreference to the following detailed description of specific embodimentsin connection with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings form part of the present specification and areincluded to further demonstrate certain aspects of the presentinvention. The invention may be better understood by reference to one ormore of these drawings in combination with the detailed description ofspecific embodiments presented herein.

FIG. 1 shows a diagram of an EC-E sensor in accordance with embodimentsof the present invention;

FIGS. 2A-2C show a bare sensor, a sensor after a metal deposition, and asensor after a polymer deposition, in accordance with embodiments of thepresent invention;

FIGS. 3A-3G show diagrams of EC-E sensors used in differentapplications, in accordance with embodiments of the present invention;and

FIG. 4 shows a graph of an output of the EC-E sensor in accordance withembodiments of the present invention.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The invention and the various features and advantageous details areexplained more fully with reference to the non-limiting embodiments thatare illustrated in the accompanying drawings and detailed in thefollowing description. Descriptions of well known starting materials,processing techniques, components, and equipment are omitted so as notto unnecessarily obscure the invention in detail. It should beunderstood, however, that the detailed description and the specificexamples, while indicating embodiments of the invention, are given byway of illustration only and not by way of limitation. Varioussubstitutions, modifications, additions, and/or rearrangements withinthe spirit and/or scope of the underlying inventive concept will becomeapparent to those skilled in the art from this disclosure.

The present invention comprises systems and methods for integratedelectrochemical and electrical detection. In one embodiment, the presentinvention integrates electrochemical and electrical (EC-E) sensingelements into a single device operable to simultaneously performelectrochemical and electrical detection, thus providing newcapabilities compared to the single detection mode typically provided byexisting sensors. The EC-E sensors disclosed herein provide uniqueselectivity features for real-time analyte detection in liquids, gases,cultures, tissues, and the like.

In one embodiment, an EC-E sensor may be able to detect an analyteeither via electrochemical current changes (ΔI_(ec)) of a conducting orsemiconducting material, conductance changes of the conducting orsemiconducting material (ΔG), or a combination of both. The combinationof both parameters (ΔI_(ec), ΔG) is particularly advantageous because itenhances selectivity for detection of analytes in complex matrices, evenin the presence of interferants with much higher concentrations than theconcentration of the analyte. In some embodiments, a nanoscale versionof the EC-E sensor may allow for the detection of very lowconcentrations of analytes.

FIG. 1 shows a diagram of an EC-E sensor in accordance with embodimentsof the present invention. The EC-E sensor may include a pair ofasymmetric working electrodes WE1 and WE2 fabricated on a silicon chipor other suitable substrate. In one embodiment, electrodes WE1 and WE2may have different surface areas, and may be separated by a gap varyingfrom, for example, microns to nanometers. For example, WE2 may have alarger area compared to WE1. The surface area ratio (WE2/WE1) isadvantageous when it becomes necessary to decrease a contribution ofelectrochemical and capacitive currents from WE1 (I_(1,ec)) on the draincurrent (I₁) taken from WE1, where I₁ may be approximately equal toI_(d), which may be directly proportional to the conductance (G).Further, the surface area ratio (WE2/WE1) may increase anelectrochemical product concentration produced on WE2, and thus it mayimprove the sensitivity to electrochemical current obtained from WE2(I_(2,ec)). In operation, WE1 and WE2 may represent source and drain(working) electrodes. A bias potential (V_(b)) may be applied betweenWE2 and WE1.

The EC-E sensor may also include a counter electrode (CE) to close theelectrical circuit responsible for the electrochemical currents. Theamplifier (A) of FIG. 1 represents part of the bipotentiostat circuitused to apply potential perturbation on WE1, which is measured against areference electrode (RE).

Referring again to FIG. 1, a conducting or semiconducting material maybridge the two electrodes. Examples of conducting material includeconducting polymers, metal oxides, nanostructures (e.g., nanotubes,nanowires, nanoparticles, nanorods, nanobelts, nanoparticles, ormolecularly imprinted materials). Alternatively or in addition to theabove, conducting materials may include composites made of polymers andconducting or semiconducting materials. The conducting material mayallow for the detection of electrical current through the materialbetween the two electrodes WE1 and WE2 under a bias voltage (V_(b)).

The sensibility of conductance changes on the conducting orsemiconducting material may be increased with a higher surface to volumeratio. This situation is reached when small but continuous and stableamounts of conducting material are immobilized or deposited into thegap. For example, use of few polymer strands, nanowires and nanotubesallows detection of conductance changes from concentrations of analytesas low a pM.

Conductivity measurements of the conducting or semiconducting materialmay also be performed through a drain current (I_(d)) from firstelectrode (WE1). An electrolyte may be provided to the device may giveelectrolytic conductance to the device. The supporting electrolyte maybe liquid, polymer, semi-liquid or solid and may be composed of ionicliquids or solid or of gels or aqueous or organic ionic solutions. Thesupporting electrolyte may be held by a cell in intimate contact withthe device surface. The second electrode (WE2) may be used to determinethe electrochemical reduction/oxidation of analytes or analytederivatives. An electrochemical potential (E1=V_(g)), may be appliedbetween the drain electrode (WE1) and a reference electrode (RE) coupledto a supporting electrolyte. Moreover, V_(g) may be gated through thesupporting electrolyte from the reference electrode (RE) andelectrochemical measurements may be monitored from a differentialcurrent between the electrodes determined by:I _(2,ec) =I ₂ −I _(d)  Eq. 1where I₂ is this the current from WE2 as pictured in FIG. 1.

The sensitivity of the EC-E sensor may be adjusted and the selectivitymay be further improved by optimizing, for example, the geometry anddimension of the electrodes, the length of the gap, amount and geometryof conducting material bridging the gap, chemical modification, as wellas gate and bias potential control. For example, the geometry anddimension of the WE1 and WE2 electrodes, and in particular, the arearatio (WE2/WE1), may be altered and improved through an electrochemicalselective deposition of metal on the second electrode (WE2). Severalmetals such as gold, platinum, palladium, mercury, nickel, silver,copper, cadmium, zinc, etc. may be suitable. By adjusting the geometryand dimension of WE1 and WE2, the electrodes' roughness and area mayincrease and allow for a reduction of the gap size from few micrometersto a few hundreds or a few nanometers.

FIGS. 2A and 2B show optical back and dark field images of a devicebefore and after a metal electrodeposition of gold to enlarge thesurface area of WE2, respectively. FIG. 2C shows the device of FIG. 2Aafter a polymer deposition. The higher brightness shown in FIG. 2Bindicates increasing roughness of the WE2. It should be noted that thegap between WE1 and WE2 decreases in size as the surface area of WE2increases. In some embodiments, smaller gaps between WE1 and WE2 mayprovide better sensitivity for electrical detection although the exactdimensions may depend upon the particular application.

The EC-E selectivity enhancement may vary based on the properties of theconducting material across the two electrodes WE1 and WE2.Alternatively, modification of the conducting material, electrodesurface, chip surface, substrate surface, or the use of a supportingelectrolyte with redox mediator molecules or other organic or biologicalrecognizing elements, such as, but not limited to, cyclodextrins, crownethers, peptides, proteins, enzymes, antibodies, aptamers, nucleic acidsand peptide nucleic acids able to interact chemically orstereo-selectively with the analyte may be used to enhance theselectivity of the EC-E sensor. In one respect, the supportingelectrolyte may be liquid or semi-solid or solid and chemically modifiedto avoid interferents.

In one embodiment, the present invention provides for the integration ofmany EC-E sensors on single chip or substrate. For a single analytedetection, even when materials and modification of the chip is uniformall over its multiple parallel devices, gated and biased potentialcontrol on different devices allows obtaining a combination of pair ofconductance and electrochemical signals (ΔI_(ec), ΔG) that ensuresdiscrimination of analyte of interest in complex matrices.

FIGS. 3A-3G show diagrams of several reaction pathways that may beaccounted and applied to EC-E detection in liquid or gas phasesaccording to certain embodiments of the present invention. The followingoutlines the type of detection, the analyte, and the effect on theconducting or semiconducting material.

Case A: Independent Electrical-Electrochemical (E-EC) Detection

Referring to FIG. 3A, when analyte A is electrochemically active andirreversible arrives to the device surface, the analyte may modify theconductance of the conducting or semiconducting material (“conducting orsemiconducting bridge”) and may be electrochemically irreversiblereduced or oxidized on WE2, providing independent drain current (I_(d))and electrochemical current (I_(2,ec)) changes. One example is thedetection of ascorbic acid.

Case B: Dependent Electrical-Electrochemical (E-EC) Detection

Referring to FIG. 3B, analyte A may be chemically converted to B in theconducting or semiconducting material and may electrochemically oxidizeor reduce to another product C or revert back to B (if it iselectrochemical reversible species). Chemical conversion of A to B maybe induced by chemical modification of the conducting or semiconductingbridge or when conducting or semiconducting bridge native material issensitive to redox changes from A.

Case C: Dependent Pure Electrical-Electrochemical (E-EC) Detection

Referring to FIG. 3C, analyte A may be oxidized or reducedelectrochemically (EC detection) and the electrochemical product B maybe detected on the conducting material (E detection). For example thisreaction pathway may be used to detect nitro-explosives that produceintermediate reduction products that can oxidize or reduce theconducting or semiconducting material bridge. Additionally oralternatively, the detection of electroactive compounds of analyte Awhich may include reversible or quasi-reversible redox features inpresence of interferences that are also electrochemically active (A′)but irreversibly oxidized or reduced. Under this condition, only theelectrochemical active product (B) coming from analyte of interest (A)may be electrically detected. For example, low dopamine concentrations(ranging from about a hundreds nM—to about a few micromolar range) canbe detected in presence of high concentrations (mM range) of ascorbicacid, uric acid or other similar interferents. This detection scheme isreferred to as an electrochemical-assisted electrical detection.

Case D: Chemical Mediated Electrochemical Electrical (EC-E) Detection

Referring to FIG. 3D, analyte A may be chemically transformed withassistance of mediator M, and then EC and E detected as described inFIGS. 3A-C described above. The chemical mediator may be dissolved inthe supporting electrolyte (SE) or immobilized on the electrodes or chipsurface. In one respect, analyte A may be acetone and may be detectedusing hydroxylamine as a mediator to produce an electrochemically activeoxime derivative.

Case E: Redox Catalyst Mediated Electrochemical Electrical (EC-E)Detection

Referring to FIG. 3E, analyte A may be a catalyst target. An inorganicor biological catalyst may be chemically wired to the larger electrode(e.g., WE2) which may pump electrons for the regeneration of thecatalyst. The catalyst byproduct may be detected on the conducting orsemiconducting material, where the sensitivity for detection may beincreased due to the catalytic effect. It is noted that a combination ofcatalysts may widen this application. For example, detection ofaldehydes and alcohols may be made using quino-dehydrogenasesimmobilized on WE2. These enzymes produce acid products that canincrease the conductance of pH sensitive conducting material.

Case F: Recognizing Element Mediated Electrochemical Electrical (EC-E)Detection

Referring to FIG. 3F, electrodes and conducting material may be modifiedwith an organic molecule, biomimic, or biological recognizing elementwhich may selectively trap an analyte that may be electrochemicallyactive. The active recognizing layer on WE2 serves as a preconcentratorof the analyte, which may be electrochemically oxidized or reduced. Therecognition of the analyte on the conducting or semiconducting materialmay induce conformational, charge, or pH changes that may be transducedas a change in conductance. This particular case can be applied to, forexample, the detection of heavy metal ions using peptides as probes.

Case G: Label-Dependent Electrochemical Electrical (EC-E) Detection

Referring to FIG. 3G, commercially available enzyme-labeled fordetection of many hormones and tumor markers used in immunologicalassays combined with the application of EC-E detection may improvedetection performance and to simplify instrumentation. Probes labeledwith commonly used enzymes such as peroxidase and alkaline phosphate maybe used to detect enzymatic products from antibodies immobilized on theEC-E devices which may have include a incubation of the sample. Afterrinsing and addition of enzyme reactants, the presence of enzyme may bedeveloped by electrochemical detection of enzymatic products andconductance change due to oxidation of the conducting or semiconductingmaterial. In cases where an unlabeled probe is immobilized on theconducting material, and in particular in the area bridging WE1 and WE2,the conductance changes may be detected directly during sampleincubation. Later EC-E detection may subsequently be performed.

In one embodiment, a number of EC-E sensors may be applied to a multipleanalyte detection in liquid and gas phases. Because integration of manydevices may be achieved in on single chip, simultaneous monitoring ofmultiple analytes may be achieved by adjusting the chemical modificationas well as gated and biased potentials. Detection of analytes in liquidphase involved delivery of the sample through injections to bath cell orthrough a microfluidic system, while detection of chemical vaporscomprise diffusion gases through a supporting electrolyte layer.

Example

The following example is included to demonstrate specific embodiments ofthis disclosure. It should be appreciated by those of skill in the artthat the techniques disclosed in the example that follows representtechniques discovered by the inventors to function in the practice ofthe invention, and thus can be considered to constitute specific modesfor its practice. However, those of skill in the art should, in light ofthe present disclosure, appreciate that many changes can be made in thespecific embodiments which are disclosed and still obtain a like orsimilar result without departing from the scope of the invention.

An illustrative, non-limiting experiment demonstrating the capability ofEC-E nanosensor to detect the neurotransmitter dopamine (Dpm) inpresence of its mayor physiological, ascorbic acid (AA), at aconcentration level three orders of magnitude higher is shown. Referringto FIG. 4, the time course of EC-E sensor made of conducting bridge ofpolyaniline (e.g., as shown in FIG. 2C) is shown. Electrochemicalcurrent (I_(2,ec)) and drain (I_(d)) current are monitoredsimultaneously towards the injection of a supporting electrolyte (50 mMH₂SO₄), AA (1 mM), and Dpm (710 nM, 610 nM and 5 μM, respectively). Itis noted that the voltages used in this examples are as follows:V_(g)=E1=200 mV vs Ag/AgCl and E2=450 mV vs Ag/AgCl.

Drain current (I_(d)) and electrochemical current from WE2 (I_(ec,2))are simultaneously recorded during successive injections of theneurotransmitter “dopamine” (Dpm) (nanomolar (nM) or micromolar (uM)range) in the presence of three orders of magnitude higher concentrationof ascorbic acid (AA). The experiments resembles physiological AA/Dpmconcentration ratio. Initial injections of supporting electrolyte areperformed to monitor stability of conducting bridge towards injections.No significant changes are observed due to injection and mechanicalstirring itself. After that, AA concentration was injected to reachmilimolar (mM) range. An increase of I_(d) is observed in parallel withan increase of I_(2,ec). The increase of I_(2,ec) may be due toirreversible oxidation of AA to dehydroascorbic. The cause of I_(d)changes may be due to the reduction of the polymer. Given the currentexperimental conditions, reduction of the conductor material istransduced into an increase of conductance (observed as importantincrease in I_(d) over the time). This is an example of Case Apreviously described in the application cases.

Next, injections of Dpm performed after AA do not produce significantchanges of electrochemical component current (I_(2,ec)) sinceelectrochemical detection may not be sensitive to oxidation of hundredof nanomolar (nM) or micromolar (uM) range of Dpm. However, theelectrochemical products of Dpm (dopaminoquinones, DQ) have an importanteffect on the conducting material, and thus I_(d). DQ molecules are ableto oxidized the conducting polymer material, and counteracts thereducing effect of AA, the mayor component in the media. Detection on amicromolar concentration change of Dpm are clearly observed by a sharpdecrease of I_(d), while detection of hundred of nanomolar concentrationchanges of Dpm may be less evident and may require better stabilizationof baseline conditions to be addressed. This is an example ofEC-assisted E detection described above.

Concentrations of a neurotransmitter three order of magnitude smallerthan its mayor physiological interferent (AA) can be easily andcontinuously detected with the sensor of the present disclosure.

All of the methods disclosed and claimed herein can be executed withoutundue experimentation in light of the present disclosure. While themethods of this disclosure may have been described in terms of preferredembodiments, it will be apparent to those of ordinary skill in the artthat variations may be applied to the methods and in the steps or in thesequence of steps of the method described herein without departing fromthe concept, spirit and scope of the disclosure. All such similarsubstitutes and modifications apparent to those skilled in the art aredeemed to be within the spirit, scope, and concept of the disclosure asdefined by the appended claims.

The invention claimed is:
 1. An electrochemical-electrical (EC-E) sensorcomprising: a first electrode fabricated on a substrate; a secondelectrode fabricated on the substrate and spaced apart from the firstelectrode; a bridging material coupling the first electrode to thesecond electrode; an electrolyte; a counter electrode; and a referenceelectrode; and wherein at least one of the electrodes is connected to anelectronic circuit for electrochemical-electrical control and/ormeasurement during use, and where a surface area ratio between thesecond electrode and the first electrode allows an electrochemicalprocess taking place on the second electrode and electrical propertiesbetween the first and second electrodes to be controlled and/or measuredsimultaneously.
 2. The sensor of claim 1, wherein the first electrode isconnected to an electronic circuit for applying a potential perturbationto the first electrode during use.
 3. The sensor of claim 2, wherein theelectronic circuit is a biopotentiostat.
 4. The sensor of claim 1,wherein the counter electrode is fabricated on the substrate.
 5. Thesensor of claim 1, wherein the reference electrode is fabricated on thesubstrate.
 6. The sensor of claim 1, wherein the bridging material isfabricated on the substrate.
 7. The sensor of claim 1, furthercomprising a third electrode placed apart from the first and secondelectrodes.
 8. The sensor of claim 7, wherein the third electrode isemployed for electrochemical control and/or measurement during use. 9.The sensor of claim 7, wherein the first and second electrodes areemployed for conductance measurement during use.
 10. The sensor of claim7, wherein the electronic circuit is a tripotentiostat.
 11. The sensorof claim 1, wherein the bridging material comprises a polymer, Si, GaAs,a metal oxide, and other organic and inorganic semiconductors, ananostructure, a molecularly imprinted material, and composites made ofpolymers and conducting or semiconducting materials.
 12. The sensor ofclaim 1, wherein the bridging material comprises at least one nanotube,nanowire, nanoparticle, nanorod, or nanobelt.
 13. A method comprising:providing an EC-E sensor of claim 1 including a conducting bridge madefrom a conducting or semiconducting material; providing an analyte;detecting a catalyst byproduct; determining a conductance and/orelectrical current of the conducting or semiconducting material;determining an electrochemical signal; and detecting the analyteemploying the conductance and the electrochemical signal.
 14. The methodof claim 13, wherein the conductance and/or electrical current ismeasured using the first electrode.
 15. The method of claim 13, whereinthe electrochemical signal is measured using the second electrode. 16.The method of claim 13, wherein the step of providing the EC-E sensorfurther comprises adjusting a surface area ratio between the secondelectrode and the first electrode to optimize performance of the EC-Esensor.
 17. The method of claim 13, wherein the analyte comprises amolecule in gas phase.
 18. The method of claim 13, wherein the analytecomprises a molecule in liquid phase.